The Chemoprevention Branch of the Division of Cancer Prevention and Control at the National Cancer Institute directs a program to identify and develop drugs for human use that will prevent, ala, or reverse the progression of cellular dysplasia (e.g. intraepithelial neoplasia) to invasive cancer. Part of the drug research and development process involves preclinical toxicology studies. These studies are performed under Good Laboratory Practices according to guidance documents published by the Food and Drug Administration and are used to support Investigational New Drug applications and eventually New Drug Applications to the FDA for the marketing approval of cancer chemopreventive agents. Dehydroepiandrosterone (DHEA) is a major steroid precursor secreted by the adrenal cortex. Inhibitory activity against glucose-6- phosphatedehydrogenase (G6DPH) and protein isoprenylation may help prevent neoplastic proliferation and transformation. Exogenously administered DHEA has efficacy as a chemopreventive agent in a number of carcinogenesis models but estrogenic and androgenic effects seen in preclinical safety studies are a concern for human chemoprevention trials. DHEA analog 8354 (fluasterone) is a fluorinated derivative of DHEA that may be a more potent chemopreventive agent without the hormonal side effects of DHEA. The contractor shall conduct 2 comparative endocrinology studies in rats and dogs of the effects of DHEA and DHEA-F particularly on the mammary and prostate tissues. Agents shall be administered for 4 weeks. Endpoints shall include hormonal measurements, histopathology, and hormone receptor measurements.